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儿童B细胞急性淋巴细胞白血病lncRNAs-mRNAs共表达网络:一项初步研究

lncRNAs-mRNAs Co-Expression Network Underlying Childhood B-Cell Acute Lymphoblastic Leukaemia: A Pilot Study.

作者信息

Affinito Ornella, Pane Katia, Smaldone Giovanni, Orlandella Francesca Maria, Mirabelli Peppino, Beneduce Giuliana, Parasole Rosanna, Ripaldi Mimmo, Salvatore Marco, Franzese Monica

机构信息

IRCCS SDN, Via E. Gianturco 113, 80143 Napoli, Italy.

Department of Paediatric Hematology-Oncology, Santobono-Pausilipon Hospital, 80143 Naples, Italy.

出版信息

Cancers (Basel). 2020 Sep 2;12(9):2489. doi: 10.3390/cancers12092489.

Abstract

Long non-coding RNAs (lncRNAs) are emerging as key gene regulators in the pathogenesis and development of various cancers including B lymphoblastic leukaemia (B-ALL). In this pilot study, we used RNA-Seq transcriptomic data for identifying novel lncRNA-mRNA cooperative pairs involved in childhood B-ALL pathogenesis. We conceived a bioinformatic pipeline based on unsupervised PCA feature extraction approach and stringent statistical criteria to extract potential childhood B-ALL lncRNA signatures. We then constructed a co-expression network of the aberrantly expressed lncRNAs (30) and protein-coding genes (754). We cross-validated our in-silico findings on an independent dataset and assessed the expression levels of the most differentially expressed lncRNAs and their co-expressed mRNAs through ex vivo experiments. Using the guilt-by-association approach, we predicted lncRNA functions based on their perfectly co-expressed mRNAs (Spearman's correlation) that resulted closely disease-associated. We shed light on 24 key lncRNAs and their co-expressed mRNAs which may play an important role in B-ALL pathogenesis. Our results may be of clinical utility for diagnostic and/or prognostic purposes in paediatric B-ALL management.

摘要

长链非编码RNA(lncRNA)正成为包括B淋巴细胞白血病(B-ALL)在内的各种癌症发病机制和发展过程中的关键基因调节因子。在这项初步研究中,我们使用RNA测序转录组数据来识别参与儿童B-ALL发病机制的新型lncRNA-mRNA协同对。我们构思了一种基于无监督主成分分析(PCA)特征提取方法和严格统计标准的生物信息学流程,以提取潜在的儿童B-ALL lncRNA特征。然后,我们构建了异常表达的lncRNA(30个)和蛋白质编码基因(754个)的共表达网络。我们在一个独立的数据集中对我们的计算机模拟结果进行了交叉验证,并通过体外实验评估了差异表达最显著的lncRNA及其共表达mRNA的表达水平。使用关联有罪方法,我们基于与疾病密切相关的完美共表达mRNA(斯皮尔曼相关性)预测lncRNA的功能。我们揭示了24个关键lncRNA及其共表达mRNA,它们可能在B-ALL发病机制中发挥重要作用。我们的结果可能在儿童B-ALL管理的诊断和/或预后方面具有临床实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/583c/7564554/6b2ef7caf4f2/cancers-12-02489-g001.jpg

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